• Wed, Apr 23 2008

Gene signature found for breast cancer survival

(Photo: Breast cancer cell , courtesy www.hopeforcancer.com)

Scientists believe they have identified a gene that may be able to limit the growth of breast cancer tumors.

The US National Cancer Institute, led by geneticist Kent Hunter found in tests on mice that tumors containing the bromodomain 4  or Brd4 gene ended up 10 times smaller than ones that did not.

In typically growing cells, Brd4 is a nuclear protein that’s associated with chromatin. It apparently influences DNA replication and cell cycle progression. Because of its previously identified physical interaction with an invasiveness-suppressing GTPase activating protein called Sipa1, Hunter and his colleagues decided to delve into Brd4’s role in breast cancer.

The team then carried out research into 1,240 patients, split between five separate groups.  They found those with the Brd4 gene had much better survival rates – in some of the groups it was nearly double the rate than those without the gene.

Using Affymetrix GeneChip Mouse Genome 430 2.0 arrays, Hunter and his team found the Brd4-mediated gene expression profile or signature in mice. Nearly 150 classes of genes seem to be influenced by Brd4 expression — including some related to cellular processes such as cell cycle progression, chromatin structure, cytoskeletal remodeling, cell adhesion, and extracellular matrix functions.

They mapped these onto human Affymetrix datasets in the National Center for Biotechnology Information Gene Expression Omnibus as well as the Dutch Rosetta cohort, which used a different microarray platform. Several hundred human genes had expression profiles that were similar to those in Brd4 expressing mouse models. In addition, the level of Brd4 activation could predict survival for all five data sets.

It also provided clues about survival in other patient populations such as those whose cancer had not spread to their lymph nodes and those with estrogen-receptor-positive tumors.

Though the results are still preliminary, they suggest that this work may help doctors better predict each patient’s breast cancer progression. In addition, the authors noted that they are currently assessing SNP data to determine whether Brd4 polymorphisms also influence breast cancer progression and prognosis.

“The results of this study and other work in our laboratory suggests that people with inherited differences in Brd4 and the proteins that it induces have a genetic predisposition for developing cancer metastasis,” Hunter said. “A better understanding of this gene may lead to improved methods of diagnosing and treating cancer.”

Elaine Warburton  www.geneticsandhealth.com

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